The long-term goal of the proposed research program is to determine the effects of pharmacologic agents on erythroid cell proliferation and growth of normal and neoplastic cells in an effort to obtain a rational basis for therapeutic intervention in hematologic diseases. In vitro culture techniques for erythroid progenitor cells will be utilized to assess the responsiveness of two early erythroid progenitor cell compartments, the so-called CFU-E and BFU-E, to agents which presumably elicit their effects by interacting with specific receptors. An initial phase of the investigation will be to evaluate a specific example of recognition-response coupling, known to play a role in erythropoiesis, that of beta-adrenergic receptors coupled to adenylate cyclase. A relatively homogeneous population of normal fetal liver erythroid cells will be compared to Friend erythroleukemia cells to determine how short-term or chronic exposure of these cells to catecholamines affects their ability to accumulate cyclic AMP. Beta-adrenergic receptor binding will be correlated with the biologic response. As a means of approaching the pharmacologic responsiveness of the earliest erythroid progenitor cell known, BFU-E colonies derived from normal and neoplastic cells will be characterized in terms of their growth responsiveness to selected pharmacologic agents such as beta-adrenergic agonists, steroids, and prostaglandins. These agents have already been demonstrated to affect the CFU-E compartment in the presence of erythropoietin. Finally, it is postulated that erythroid cells in the myeloproliferative disease, polycythemia vera, may respond to pharmacologic agents in much the same manner as erythroid cells infected with a polycythemia-inducing strain of Friend murine virus. Experiments will be carried out to assess BFU-E and CFU-E colony formation in these disorders in response to selected pharmacologic agents. Data obtained from these studies should allow certain inferences to be made regarding the receptors present on erythroid progenitor cells which respond to therapeutic manipulation.